Process for producing vitamin A aldehyde and intermediate for producing the same

Abstract

There are disclosed an alcohol derivative of formula (1): wherein Ar is an optionally substituted aryl group and R is a straight or branched C1-C3 lower alkyl group, and the wavy line depicted by indicates a single bond and stereochemistry relating to a double bond bound therewith is E or Z or a mixture thereof, and a process for producing the same and a process for producing Vitamin A aldehyde using the same.

What is claimed is:  
     
       1. A method for producing an alcohol derivative of formula (1):                    
       wherein 
       Ar is an aryl group, which may be substituted with a substituent group selected from  
       a C1-C5 alkyl group, a C1-C5 alkoxy group, a halogen atom and a nitro group,  
       R is a straight or branched C1-C3 lower alkyl group, and the wavy line depicted by                    
        indicates a single bond and stereochemistry relating to a double bond bound therewith is E or Z or a mixture thereof,  
       which comprises reacting a diol derivative of formula (2):                    
       wherein Ar and the wavy line represent the same as defined above, with a lower alcohol of formula: 
       
         
           ROH  (3)  
         
       
       wherein R is a straight or branched C1-C3 lower alkyl group, in the presence of an acid catalyst.  
     
     
       2. A method for producing an aldehyde derivative of formula (4):                    
       wherein 
       Ar is an aryl group, which may be substituted with a substituent group selected from  
       a C1-C5 alkyl group, a C1-C5 alkoxy group, a halogen atom and a nitro group,  
       R is a straight or branched C1 14  C3 lower alkyl group, and the wavy line depicted by                    
       indicates a single bond and stereochemistry relating to a double bond bound therewith is E or Z or a mixture thereof, 
       which comprises reacting an alcohol derivative of formula (1):                    
       wherein Ar, R and the wavy line represent the same as defined above, with an oxidizing agent optionally in the presence of a catalyst. 
     
     
       3. A method according to  claim 2 , which further comprises the step of reacting said aldehyde derivative of formula (4), with a base to produce Vitamin A aldehyde of formula (5):                    
       wherein the wavy line depicted by “” indicates a single bond and stereochemistry relating to a double bond bound therewith is E or Z or a mixture thereof. 
     
     
       4. A method for producing Vitamin A aldehyde of formula (5):                    
       wherein the wavy line depicted by                    
       indicates a single bond and stereochemistry relating to a double bond bound therewith is E or Z or a mixture thereof, which comprises the steps of: 
       reacting a diol derivative of formula (2):                    
        wherein  
       Ar is an aryl group, which may be substituted with a substituent group selected from  
       a C1-C5 alkyl group, a C1-C5 alkoxy group, a halogen atom and a nitro group, and the wavy line represents the same as defined above, with a lower alcohol of formula:  
       
         
           ROH  (3)  
         
       
       wherein R is a straight or branched C1-C3 lower alkyl group, in the presence of an acid catalyst, to produce an alcohol derivative of formula (1):                    
       wherein Ar, R and the wavy line represent the same as defined above,  
       reacting the alcohol derivative of formula (1) with an oxidizing agent optionally in the presence of a catalyst to produce an aldehyde derivative of formula (4):                    
       wherein Ar, R and the wavy line represent the same as defined above, and reacting the aldehyde derivative of formula (4) with a base.  
     
     
       5. A method according to  claim 1  or  4 , wherein said acid catalyst is a Lewis acid or a Brφnsted acid. 
     
     
       6. A method according to  claim 1  or  4 , wherein said acid catalyst is stannous chloride, stannic chloride, zinc chloride, ferric chloride, boron trifluoride ether complex, scandium triflate, hydrogen bromide, hydrogen chloride, sulfuric acid, p-toluenesulfonic acid, benzenesulfonic acid, methanesulfonic acid, benzoic acid, triphenylphosphine hydrobromide, pyridine hydrochloride, phosphotungstic acid hydrate, phosphomolybdic acid hydrate, silicotugstic acid hydrate, or an acidic ion exchange resin having a terminal sulfonic acid group. 
     
     
       7. A method according to  claim 2 , or  4  wherein said oxidizing of the alcohol derivative of formula (1) comprises: 
       (a) subjecting the alcohol derivative (1) to contact with a metal oxidant, or  
       (b) subjecting the alcohol derivative (1) to contact with a sulfoxide compound, a sulfoxide-activating compound and optionally a base, or  
       (c) subjecting the alcohol derivative (1) to contact with a sulfide compound, a halogenating agent and a base, or  
       (d) subjecting the alcohol derivative (1) to contact with an aldehyde in the presence of a catalyst selected from an aluminum alkoxide or aryloxide, and a boron compound, or  
       (e) subjecting the alcohol derivative (1) to contact with an oxygen in the presence of a catalyst selected from  
       platinum, a catalyst comprising 2,2,6,6-tetramethylpiperidine 1-oxyl and copper chloride, a catalyst comprising tris(triphenylphosphine)ruthenium and hydroquinone chloride, and a catalyst comprising tetrapropylammonium perruthenate and molecular sieves 4A.  
     
     
       8. A method according to  claim 3  or  4 , wherein said base is an alkali metal hydroxide, an alkali metal hydride, an alkali metal alkoxide, a bicyclic tertiary amine compound, proazaphosphatrane and 1,8-bis(dimethylamino)naphthalene. 
     
     
       9. A method according to  claim 3  or  4 , wherein the base is sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium hydride, potassium hydride, sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, sodium t-butoxide, potassium t-butoxide, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, proazaphosphatrane or 1,8-bis(dimethylamino)naphthalene.